This application is to meet the needs of 12 NIH-funded research projects on the BU Medical Campus (BUMC) and surrounding area for mass spectrometry instrumentation. These NIH funded-projects require state-of-the- art proteomics, glycomics or glycoproteomics analysis capabilities. The needs of the community of NIH funded investigators include (i) bottom-up proteomics of cross-linked proteins and post-translationally modified proteins, (ii) combined glycomics and proteomics from histological tissue slides; (iii) bottom-up glycoproteomics. There are no instruments available on the Boston University Medical Campus with the combination of sensitivity, speed and resolution necessary for such analyses. Accordingly, the present request is to replace existing obsolete instrumentation with a new Thermo-Fisher Scientific Q-Exactive HF LC/MS system. This new instrument produces high resolution, high mass accuracy tandem mass spectra that is essential for interpreting cross-linked proteins and post-translationally modified proteins. It extends the capability of traditional triple quadrupole mass spectrometers by producing high resolution and mass accuracy targeted mass spectral data that are crucial for quantifying changes in abundances of modified proteins in biological systems. It has unique tandem MS multiplexing capability that leverages ultra-performance chromatography systems now available. It has powerful data independent analysis features, including precursor ion multiplexing, that enable non-targeted quantification of modified peptides. It is very robust and well-suited to high-throughput analyses. Major user project areas include: (1-3) bottom-up proteomics analysis of cross-lined proteins or post-translationally modified proteins; (4-7) combined glycomics and proteomics of histological tissue; (8, 9) bottom-up glycoproteomics. In summary, the requested instrument system is necessary for the success of the described group of major and minor users on the BU Medical Campus and surrounding area.